In this section, you can access to the latest technical information related to the FUTURE project topic.

Identification of 1?phenyl?4?cyano?5?aminopyrazoles as novel ecdysone agonists by virtual screening, structural optimization, and biological evaluations

A series of novel ecdysone agonists 1?phenyl?4?cyano?5?aminopyrazoles were discovered through combining structured?based virtual screening, structural optimization and biological evaluations. A further structural optimization of VS14 were provided as the basis for designing new ligands with improved activity. The most potent ligand I10 (IC50=0.64 ??) showed higher binding activity against Plutella xylostella ecdysone receptor than tebufenozide (RH?5992, IC50=0.85 ??).Ecdysteroids initiate the molting process in insects by binding to the ecdysone receptor (EcR), which is a promising target for identifying insect growth regulators. This paper presents an in silico/in vitro screening procedure for identifying new EcR ligands. The three?step virtual screening procedure uses a three?dimensional pharmacophore model, docking and Molecular Mechanics/Poisson?Boltzmann Surface Area (MM/PBSA) rescoring routine. A novel hit (VS14) with good binding activity against Plutella xylostella EcR was identified from a library of over 200 000 chemicals. Subsequently, the 1?phenyl?4?cyano?5?aminopyrazole scaffold and twelve ecdysone agonists were synthesized. Their IC50 values against Plutella xylostella EcR ranged from 0.64 to 23.21 ?M. Furthermore, a preliminary analysis of the structure?activity relationship for novel scaffolds provided a basis for designing new ligands with improved activity.

» Author: Xueping Hu, Xiaojuan Ma, Jialin Cui, Haishan Liu, Bin Zhu, Jin Xie, Pei Liang, Li Zhang

» Reference: doi:10.1111/cbdd.13772

» Publication Date: 07/08/2020

» More Information

« Go to Technological Watch



AIMPLAS Instituto Tecnológico del Plástico

C/ Gustave Eiffel, 4
(València Parc Tecnològic) - 46980
PATERNA (Valencia) - SPAIN

PHONE

(+34) 96 136 60 40

EMAIL

Project Management department - Sustainability and Industrial Recovery
life-future-project@aimplas.es